Transcription Project

Sivasangari Balakrishnan, Ph.D

**** * ******* ******,

Apt#2B, Chicago

Illinois-60657

Mob No: +1-773-***-****

Email: adci3r@r.postjobfree.com

Education

Ph.D., in Biochemistry (2010-2016) at Bharathidasan University, India.

M.Phil, in Biochemistry (2008 -2009) with first class with distinction at SASTRA University, India.

M.Sc., in Biochemistry (2006-2008) with first class with distinction at SASTRA University, India.

B. Sc., in Biochemistry (2003-2006) with first class with distinction at Mother Teresa University, India.

Research Interests

Understanding epigenetics in transcriptional regulation of physiological/pathophysiological states of the organism.

Evaluating cell signaling axis involved in cellular function specifically different levels of development of an organism and it changes in the disease state.

Exploring the molecular mechanisms at the gene level and finding therapeutic targets to restore insulin in the context of diabetes mellitus.

Research Experience

Worked as a research fellow in the Department of Biotechnology, India sponsored project “Effect of Acute inflammation on histone H3 modifications in Rat testis and its implications in Testicular Steroidogenesis”.

In this project, we have characterized the molecular mechanisms of the inhibitory role of TNF- α on testicular steroidogenesis and gonadal functions. We found that TNF-α suppressed histone H3 acetylation as well as methylation, and concomitantly, increased the histone deacetylases activity in Leydig cells. We also identified DAX1 as the key mediator of TNF-α effect and demonstrated that knockdown of DAX1 restored normal steroidogenesis.

Worked in another independent Department of Science & Technology sponsored project “Role of Class II histone deacetylases in the regulation of insulin gene transcription”.

Summary of Ph.D. Thesis

Study on glucose-dependent expression of PAX6 and HDAC7 in the regulation of pancreatic β- cell function

Glucose regulation of β-cell function depends on several complementary mechanisms that include recruitment of transcription factors to regulatory sites, histone modifications and initiation of transcriptions. Hence, dysregulation of any of the above events can interfere with β-cell function results in diabetes. Therefore, the investigation of the mechanisms involved in the regulation of β cell-enriched transcription factors and epigenetic modifications by glucose will be helpful in the design of novel clinical interventions to diabetes mellitus. In the present study, we demonstrate that glucose-dependent suppression of paired box6 (Pax6) and histone deacetylase 7 (HDAC7) regulates beta-cell survival and insulin secretion. Here, Among Kruppel like factor family, Hairy like enhancer split and paired box family, Pax6 significantly suppressed with acute stimulation of glucose when compared to low glucose treated cells. Next, we found that glucose-mediated activation of PKC and JNK/p38 MAPK pathway involved in the down-regulation of Pax6 expression in pancreatic beta-cells. We screened all class of cyclins and among them, Cyclin A1, Cyclin D1, Cyclin E, Cyclin G1 significantly increased their protein expression, in turn, Pten significantly decreased upon acute stimulation of glucose. siRNA specific suppression of Pax6 in acute stimulation of glucose decreases the expression of PTEN, concurrently increasing cyclins A1/D1 as well as increased cell viability. On the other hand, high glucose significantly increased histone H3 acetylation at 9,14,18,26,57 positions and concurrently decreased total HDAC activity. Further, we screened all class of HDACs, we found that HDAC7 mRNA expression was significantly down-regulated in high glucose treated pancreatic beta-cells. The experiments from siRNA mediated knockdown suggest that PAX6 reduced HDAC7 expression in response to glucose concentrations. Furthermore, glucose deliberately modulates cytoplasmic retention of HDAC7 by increasing phosphorylation at ser 155 through PKD1 mediated phosphorylation at ser 744 and 748 in a time-dependent manner. Knockdown of HDAC7 using siRNA significantly increased insulin mRNA expression at low glucose concentrations, suggesting its vital role in the regulation of insulin gene transcription. In conclusion, the present study reveals a novel finding that glucose-mediated suppression of Pax6 results in down-regulation of HDAC7, and these events regulate cell survival and insulin gene transcription in pancreatic beta-cells.

Publications

1.Balakrishnan S, Sadasivam M, Kannan A, Panneerselvam A, Prahalathan C*. Glucose modulates Pax6 expression through the JNK/p38 MAP kinase pathway in pancreatic β-cells. Life Sci. 2014; 109:1-7.

2.Sadasivam M, Ramatchandirin B, Balakrishnan S, Prahalathan C*. TNF-α-mediated suppression of Leydig cell steroidogenesis involves DAX-1. Inflamm Res. 2015; 64:549-56.

3.Sadasivam M, Ramatchandirin B, Balakrishnan S, Prahalathan C*. HDAC7 modulates TNF-α mediated suppression of Leydig cell steroidogenesis. Mol Cell Biochem. 2015 Apr 28.

4.Sadasivam M, Ramatchandirin B, Balakrishnan S, Selvaraj K, Prahalathan C*. The role of phosphoenolpyruvate carboxykinase in neuronal steroidogenesis under acute inflammation. Gene. 2014; 552:249-54.

5.Balakrishnan S, Kumar P, Suhasini D,Prahalathan C* - Transcription factors in the context of Diabetes Mellitus and β-cell Regeneration Review -In Communication.

6.Balakrishnan S, Kumar P, Bellur S Prabhakar*. Post Translational Modifications Contribute to Neoepitopes in Type-1 Diabetes Challenges for Inducing Antigen-Specific Tolerance. Review -In Publication process.

Fellowships & Awards

Junior and Senior Research fellowship from Department of Biotechnology, Govt. of India (2012-2014).

Best oral presentation award at 6th World Congress of Diabetes India -2015 held in Chennai, India.

Best poster presentation award at National conference GeneChem-2009, SASTRA University, India.

Abstracts presented

Sivasangari Balakrishnan, Mohanraj Sadasivam, Balamurugan Ramatchandirin, Arun Kannan. Prahalathan Chidambaram* “Glucose-dependent expression of Pax 6 regulates cell survival in pancreatic beta cells’’ at 6th World Congress of Diabetes India -2015 at Chennai.

Ramatchandirin B, Mohanraj S, Sivasangari B, Manikandan K, and Prahalathan C. Presented a poster on “A study on the role of bacterial lipopolysaccharide on histone deacetylases in rat pancreas”. National conference on endocrinology and reproduction: Innovative in reproductive biotechnology & XXXI Annual meeting of the society for reproductive biology and comparative endocrinology. Karnatak University, Dharwad, India. February 11-13, 2013.

Sivasangari B “In-vitro studies on Antioxidant capacity of Pleurotus +florida” at National conference on “Natural products in health and disease-2008 at Annamalai University, Chidambaram.

Arun Kannan, Balamurugan Ramatchandirin, Mohanraj Sadasivam, Sivasangari Balakrishnan Prahalathan Chidambaram*. Role of oxidative stress on testicular Aquaporins expression in hyperglycemic rats at 6th World Congress of Diabetes India -2015 at Chennai.

Sivasangari Balakrishnan. Glucose dependent expression of HDAC7 in the regulation of beta cell function on Midwest Clinical and Translational Research Meeting at Chicago.USA.

Conference participated

National conference on challenges and future prospects of applied research in life sciences-2015 at Bharathidasan University, India.

National Conference on “Natural products in Health and Disease -’2008”, at Annamalai University, India.

International conference on “Nanomedicine & its applications – 2007” at SASTRA University, India.

International Symposium on “Biotechnology and women Empowerment - 2006” at Mother Teresa women’s University, Kodaikanal.

Technical skills

Cell & Molecular Biology: Mammalian cell culture, RNA isolation, cDNA preparation, RT-qPCR, Mammalian cell transfection, Western blot, ELISA, Immunofluorescence, Immunoprecipitation, Cell viability assays, Liquid chromatography.

Computational skills: Gene promoter analysis, Sequence alignment, Protein homology & Ab initio modeling and visualization tools, GraphPad Prism.

Workshops participated

Hands-on training on High-Performance Liquid Chromatography and Mass spectrometry at Annamalai University, India.

National workshop on methods in InVitro Toxicology at Bharathidasan University. Tiruchirappalli.

Workshops handled

Handled a technical session in the National workshop on Basic Molecular Biological Techniques in QUEST-2013 at Bharathidasan University. Tiruchirappalli, India.

References

1.Dr. C. Prahalathan

Associate Professor

Department of Biochemistry.

Bharathidasan University

Tiruchirappalli – 620 024 Tamil Nadu, India

Telephone: 0431- 2407071(Extn. 484)

E-mail: adci3r@r.postjobfree.com (or) adci3r@r.postjobfree.com

2.Dr. K. Premkumar

Professor&Head

Department of Biomedical Science

Bharathidasan University

Tiruchirappalli – 620 024.

Tamil Nadu, India

Phone: +91-431-*******/72/74 (Ext: 432)

E-Mail: adci3r@r.postjobfree.com (or) adci3r@r.postjobfree.com

3.Dr. V. Ravikumar

Associate Professor

Department of Biochemistry

Bharathidasan University

Tiruchirappalli – 620 024

Tamil Nadu, India

Telephone: 043*-*******(Extn. 485)

E-mail: adci3r@r.postjobfree.com

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